天然产品在调节法恩类 X 受体防治非酒精性脂肪肝中的作用

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-03-14 DOI:10.1142/S0192415X24500137
Jing Wang, Na Yang, Yu Xu
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引用次数: 0

摘要

非酒精性脂肪肝(NAFLD)是一个全球关注的健康问题,发病率很高,经济负担日益加重,但官方药物仍然缺乏。法尼类固醇 X 受体(FXR)是一种核受体,是治疗非酒精性脂肪肝最有希望的药物靶点之一,它在调节胆汁酸、葡萄糖和脂质平衡以及抑制肝脏炎症和纤维化方面发挥着至关重要的作用。然而,食品药品管理局拒绝将 FXR 激动剂顺胆酸用于治疗肝纤维化,这引发了人们对 FXR 在非酒精性脂肪肝进展过程中的功能以及治疗策略的疑问。天然产品(如 FXR 调节剂)已成为非酒精性脂肪肝治疗中不良反应较少的关注焦点。抗非酒精性脂肪肝的机制似乎可作为 FXR 激动剂和拮抗剂,或参与 FXR 信号通路的激活,这表明利用天然产品靶向治疗 FXR 前景广阔。本综述探讨了 FXR 在缓解非酒精性脂肪肝中的有效机制,并总结了水飞蓟素、甘草苷、环黄芪醇、小檗碱和石膏苷等目前可用于靶向 FXR 的天然产物,这有助于药学专家开发天然靶向药物,以有效治疗非酒精性脂肪肝。
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Natural Products in the Modulation of Farnesoid X Receptor Against Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with a high prevalence and increasing economic burden, but official medicine remains unavailable. Farnesoid X receptor (FXR), a nuclear receptor member, is one of the most promising drug targets for NAFLD therapy that plays a crucial role in modulating bile acid, glucose, and lipid homeostasis, as well as inhibits hepatic inflammation and fibrosis. However, the rejection of the FXR agonist, obecholic acid, by the Food and Drug Administration for treating hepatic fibrosis raises a question about the functions of FXR in NAFLD progression and the therapeutic strategy to be used. Natural products, such as FXR modulators, have become the focus of attention for NAFLD therapy with fewer adverse reactions. The anti-NAFLD mechanisms seem to act as FXR agonists and antagonists or are involved in the FXR signaling pathway activation, indicating a promising target of FXR therapeutic prospects using natural products. This review discusses the effective mechanisms of FXR in NAFLD alleviation, and summarizes currently available natural products such as silymarin, glycyrrhizin, cycloastragenol, berberine, and gypenosides, for targeting FXR, which can facilitate development of naturally targeted drug by medicinal specialists for effective treatment of NAFLD.

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